Probing the Impact of Porosity on Swelling Kinetics of Hydrophilic Matrices

The aim of the present investigation was to understand the swelling behaviour of HPMC and PEO-based matrices and to evaluate the impact of porosity on the swelling kinetics. It was noticed that the HPMC has higher swelling rates but both undergo diffusion oriented swelling mechanism. It could also the concluded that the porosity has a marked influence in the development of gel layer on the surface of these matrices

Kinetics of exoglucanase and endoglucanase produced by Aspergillus niger NRRL 567

In this study we reported for the first time kinetics of exoglucanase (EXG) and endoglucanase (EG) from Aspergillus niger NRRL 567. The optimum pH and temperature for crude EXG and EG was found to be 3.5 and 30°C respectively. Zn2+, Ca2+, Mn2+ and Co2+ enhanced the crude activity of EXG and EG whereas Mg2+, Fe2+ and Hg2+ showed various degree of inhibitory effects. Cu2+ enhanced crude EXG activity and inhibited crude EG activity. The energy of activation (Ea) for the EXG and EG were 21.20 and 22.52 kJ mol-1, respectively. The Q10 values obtained for the EXG and EG were 1.38 and 1.4, respectively. These enzymes had lower Km value that shows their high affinity for the substrates. Overall, the studies demonstrate that these enzymes may be suitable for industrial use.Key words: Exoglucanase, endoglucanase, kinetics, characterization, Aspergillus niger NRRL 567

Corn stover-enhanced cellulase production by Aspergillus niger NRRL 567

The production of extracellular cellulases by Aspergilus niger NRRL 567 on corn stover was studied in liquid state fermentation. In this study, three cellulases, exoglucanase (EXG), endoglucanase (EG) and β-glucosidase (BGL) were produced by A. niger NRRL 567. The optimal pH, temperature and incubation time for cellulases production was found to be 3.5, 30°C and 96 h, respectively. Maximal cellulases activities were achieved with 4% corn stover, 0.1% molasses and 1% yeast sludge. To our knowledge, this is the first report on production of cellulases by using corn stover as a substrate from A. niger NRRL 567.Key words: Corn stover, yeast sludge, cellulases, Aspergi l lus niger

Formulation and In-vitro evaluation of Orodispersible tablets of Telmisartan

Orodispersible dosage forms are used for accurate dosing, enhanced bioavailability, rapid action, patient compliance, ease of administration, enhanced palatability.  Telmisartan is an antihypertensive drug which belongs to the class of Angiotensin Receptor ΙΙ antagonist. It is a poorly soluble drug (BCS class-II) and the rate of absorption is limited by the dissolution rate. The reported bioavailability of drug is about 42%. In the present study an attempt was made to develop Oral dispersible tablets of Telmisartan formulated with super disintegrating agent with superior dissolution properties. The aim is to formulate various batches of oral disintegrating tablets of Telmisartan by using different superdisintegrants such as Indion 414, Indion 234 and Kyron T 314 with different concentrations individually by using different excipients like Mannitol, magnesium stearate and aspartame. Formulations of P1 to P13 are formulated with different superdisintegrants by wet granulation technique. The tablets were evaluated for the pre-compression parameters such as bulk density, compressibility, angle of repose etc. and post compression parameters like hardness, weight variation, friability, disintegration time and in-vitro dissolution profiles. Drug content for all formulation batches i.e. P1-P13 was found to be in the range of 99.76%-102.23%. Based on the evaluation of all parameters, the formulation P5 were found to be best on the basis of following crucial factors like hardness, drug content, disintegration time (14.4 sec) and wetting time. Keywords: Superdisintegrants, Orodispersible tablet, Wet granulatio

Elucidation of the controlled-release behavior of metoprolol succinate from directly compressed xanthan gum-chitosan polymers: computational and experimental studies

The development and evaluation of a controlled-release (CR) pharmaceutical solid dosage form comprising xanthan gum (XG), low molecular weight chitosan (LCS) and metoprolol succinate (MS) is reported. The research is, partly, based upon the utilization of computational tools; in this case molecular dynamics simulations (MDs) and response surface method (RSM), in order to underpin the design/prediction and to minimize the experimental work required to achieve the desired pharmaceutical outcomes. The capability of the system to control the release of MS was studied as a function of LCS (% w/w) and total polymer (LCS and XG) to drug ratio (P:D) at different tablet tensile strengths. MDs trajectories, obtained by using different ratios of XG:LCS as well as XG and high molecular weight CS (HCS), showed that the driving force for the interaction between XG and LCS is electrostatic in nature, the most favourable complex is formed when LCS is used at 15 % (w/w) and, importantly, that the interaction between XG and LCS is more favourable than that between XG and HCS. RSM outputs revealed that the release of the drug from the LCS/XG matrix is highly dependent on both the % LCS and the P:D ratio and that the required CR effect can be achieved when using weight fractions of LCS ≤ 20% and P:D ratios ≥ 2.6:1. Results obtained from in-vitro drug release and swelling studies on the prepared tablets showed that using LCS at the weight fractions suggested by MDs and RSM data plays a major role in overcoming the high sensitivity of the controlled drug release effect of XG on ionic strength and pH changes of the dissolution media. In addition, it was found that polymer relaxation is the major contributor to the release of MS from LCS-XG tablets. Using Raman spectroscopy, MS was shown to be localized more in the core of the tablets at the initial stages of dissolution due to film formation between LCS and XG on the tablet surface which prevents excess water penetration into the matrix. In the later stages of the dissolution process, the film starts to dissolve/erode allowing full tablet hydration and a uniform drug distribution in the swollen tablet

KEYNOTE-022 part 3: A randomized, double-blind, phase 2 study of pembrolizumab, dabrafenib, and trametinib in BRAF-mutant melanoma

Background In the KEYNOTE-022 study, pembrolizumab with dabrafenib and trametinib (triplet) improved progression-free survival (PFS) versus placebo with dabrafenib and trametinib (doublet) without reaching statistical significance. Mature results on PFS, duration of response (DOR), and overall survival (OS) are reported. Methods The double-blind, phase 2 part of KEYNOTE-022 enrolled patients with previously untreated BRAF V600E/K-mutated advanced melanoma from 22 sites in seven countries. Patients were randomly assigned 1:1 to intravenous pembrolizumab (200 mg every 3 weeks) or placebo plus dabrafenib (150 mg orally two times per day) and trametinib (2 mg orally one time a day). Primary endpoint was PFS. Secondary endpoints were objective response rate, DOR, and OS. Efficacy was assessed in the intention-to-treat population, and safety was assessed in all patients who received at least one dose of study drug. This analysis was not specified in the protocol. Results Between November 30, 2015 and April 24, 2017, 120 patients were randomly assigned to triplet (n=60) or doublet (n=60) therapy. With 36.6 months of follow-up, median PFS was 16.9 months (95% CI 11.3 to 27.9) with triplet and 10.7 months (95% CI 7.2 to 16.8) with doublet (HR 0.53; 95% CI 0.34 to 0.83). With triplet and doublet, respectively, PFS at 24 months was 41.0% (95% CI 27.4% to 54.2%) and 16.3% (95% CI 8.1% to 27.1%); median DOR was 25.1 months (95% CI 14.1 to not reached) and 12.1 months (95% CI 6.0 to 15.7), respectively. Median OS was not reached with triplet and was 26.3 months with doublet (HR 0.64; 95% CI 0.38 to 1.06). With triplet and doublet, respectively, OS at 24 months was 63.0% (95% CI 49.4% to 73.9%) and 51.7% (95% CI 38.4% to 63.4%). Grade 3-5 treatment-related adverse events (TRAEs) occurred in 35 patients (58%, including one death) receiving triplet and 15 patients (25%) receiving doublet. Conclusion In BRAF V600E/K-mutant advanced melanoma, pembrolizumab plus dabrafenib and trametinib substantially improved PFS, DOR, and OS with a higher incidence of TRAEs. Interpretation of these results is limited by the post hoc nature of the analysis

A meta-analysis for the effect of prophylactic GTN on the incidence of post-ERCP pancreatitis and on the successful rate of cannulation of bile ducts

<p>Abstract</p> <p>Background</p> <p>Glyceryl trinitrate (GTN) has been shown to be able to relax the sphincter of Oddi (SO) both in animals and humans. Theoretically, the use of these compounds during and after endoscopic retrograde cholangiopancreatgraphy (ERCP) could relax the biliary and pancreatic sphincters, facilitating cannulation of common bile duct (CBD) during the procedure, or minimizing potential pancreatic outflow obstruction after the procedure. However, clinical trials evaluating the protective effect of GTN on the post-endoscopic retrograde cholangiopancreatgraphy pancreatitis (PEP) have yielded inconclusive results. This meta-analysis is to systematically assess the effect of prophylactic administration of glyceryl trinitrate (GTN) on the prevention of PEP and the effect on the cannulation of bile ducts.</p> <p>Methods</p> <p>By searching PubMed (1966 to September 2009), CENTRAL (Cochrane Controlled trials Register; issue 3, 2009) and EMBASE.com (1984 to September 2009), two independent reviewers systematically identified prospective randomized controlled trials (RCTs) detecting the effect of prophylactic GTN on the incidence of PEP and on the cannulation of bile ducts. A meta-analysis of these clinical trials was then performed.</p> <p>Results</p> <p>There are 55/899(6.1%) patients suffering PEP in the treatment group versus 95/915(10.4%) patients in the placebo group. The overall pooled risk of PEP was significantly lower in the GTN group than in the placebo group (OR 0.56, 95% CI: 0.40 to 0.79, p = 0.001). Subgroup analyses suggested that GTN administered by the sublingual form (OR 0.34,95% CI:0.16 to 0.75, p = 0.007) is more effective than transdermal route(OR 0.64,95% CI:0.40 to 1.01, p = 0.05), and the protective effect of GTN was far more obvious in the centers with high incidence of PEP (OR 0.40, 95% CI:0.24 to 0.67, p = 0.0006) than those centers with a low incidence of PEP (OR 0.75, 95% CI: 0.47 to 1.20, p = 0.22). Additionally, the meta-analysis suggests that GTN was not helpful for the cannulation of bile ducts.</p> <p>Conclusion</p> <p>We concluded that prophylactic administration of GTN may significantly reduce the incidence of PEP and not be helpful for the cannulation of bile ducts.</p